Do FLT3 mutations occur in leukemia stem cells?
A recently evolving paradigm in the field of cancer biology is that of cancer stem cells.155 If a malignancy within a given patient arises from cancer stem cells that have the capacity for self-renewal, then targeted therapies should ideally be directed against these malignant stem cells. Most of the studies validating FLT3 as a therapeutic target in AML have been carried out using either tumor tissue (marrow samples), which contain only a small proportion of malignant stem cells, or using immortalized cell lines. The finding that AML samples harboring FLT3/ITD mutations have much greater engraftment potential in the NOD/SCID mouse suggests that these mutations are usually intrinsic to the leukemia stem cell.59,105,156 However, it remains to be seen if inhibiting FLT3 has the same effect on leukemia stem cells as it does on the progeny cells with limited self-renewal potential. Hypothetically, FLT3 activating mutations could simply be an epiphenomenon. In other words, the poor prognosi
